Analysis of ACE2 Genetic Variability among Populations Highlights a Possible Link with COVID-19-Related Neurological Complications
Analysis of ACE2 Genetic Variability among Populations Highlights a Possible Link with COVID-19-Related Neurological Complications
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DOI：
10.3390/genes11070741
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发表时间：
2020-07-01
期刊：
影响因子：
3.5
通讯作者：
Cascella, Raffaella
中科院分区：
文献类型：
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作者：
Strafella, Claudia;Caputo, Valerio;Cascella, Raffaella
血管紧张素转换酶2（ACE2）已被认为是新型严重急性呼吸综合征冠状病毒2（SARS-Cov-2）的进入受体。 ACE2基因的结构和序列变异可能会影响其在不同组织中的表达，并决定对SARS-Cov-2感染和COVID-19相关表型的不同反应。本研究在代表意大利普通人群的 268 名个体中调查了 ACE2 的遗传变异性，包括单核苷酸变异 (SNV)、拷贝数变异 (CNV) 和表达定量位点 (eQTL)。该分析在意大利队列中发现了 5 个 SNV（rs35803318、rs41303171、rs774469453、rs773676270 和 rs2285666）。其中，rs35803318 和 rs2285666 在意大利人口中与全球人口中显示出显着不同的频率分布。位于并针对 ACE2 的 eQTL 分析揭示了不同脑组织中 eQTL 变异的高分布，表明 ACE2 遗传变异性与 COVID-19 患者的神经系统并发症之间可能存在联系。需要进一步的研究来阐明 ACE2 表达与 COVID-19 患者神经系统并发症易感性之间可能的关系。事实上，神经系统受累风险较高的患者可能需要不同的监测和治疗策略，以防止严重的永久性脑损伤。
Angiotensin-converting enzyme 2 (ACE2) has been recognized as the entry receptor of the novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Structural and sequence variants inACE2gene may affect its expression in different tissues and determine a differential response to SARS-Cov-2 infection and the COVID-19-related phenotype. The present study investigated the genetic variability ofACE2in terms of single nucleotide variants (SNVs), copy number variations (CNVs), and expression quantitative loci (eQTLs) in a cohort of 268 individuals representative of the general Italian population. The analysis identified five SNVs (rs35803318, rs41303171, rs774469453, rs773676270, and rs2285666) in the Italian cohort. Of them, rs35803318 and rs2285666 displayed a significant different frequency distribution in the Italian population with respect to worldwide population. The eQTLs analysis located in and targetingACE2revealed a high distribution of eQTL variants in different brain tissues, suggesting a possible link betweenACE2genetic variability and the neurological complications in patients with COVID-19. Further research is needed to clarify the possible relationship betweenACE2expression and the susceptibility to neurological complications in patients with COVID-19. In fact, patients at higher risk of neurological involvement may need different monitoring and treatment strategies in order to prevent severe, permanent brain injury.